Synthesis, characterisation and evaluation of a novel copper-64 complex with selective uptake in EMT-6 cells under hypoxic conditions

Knight, James C.; Wuest, Melinda; Saad, Fawaz A.; Wang, Monica; Chapman, David; Jans, Hans-Soenke; Lapi, Suzanne E.; Kariuki, Benson M.; Amoroso, Angelo J.; Wuest, Frank

doi:10.1039/c3dt50960e

Cited by 9 publications

(28 citation statements)

References 56 publications

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“…Larger SD across reconstructions observed with FBP algorithm for mean SUV max and mean T/B may reflect limitations of this algorithm ( 13 ), arising from applying available defaults and possible low count-rate statistics. As expected for each respective time frame and within each respective reconstruction algorithm, mean T/B >corresponding mean SUV max and the difference was statistically significant (p<0.0001 in all cases) ( 21 ).…”

Section: Discussionsupporting

confidence: 68%

Pre-clinical Positron Emission Tomography Reconstruction Algorithm Effect on Cu-64 ATSM Lesion Hypoxia

Sanghera

Wood²,

Sonoda³

et al. 2016

Mirt

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Objective:Application of distinct positron emission tomography (PET) scan reconstruction algorithms can lead to statistically significant differences in measuring lesion functional properties. We looked at the influence of two-dimensional filtered back projection (2D FBP), two-dimensional ordered subset expectation maximization (2D OSEM), three-dimensional ordered subset expectation maximization (3D OSEM) without 3D maximum a posteriori and with (3D OSEM MAP) on lesion hypoxia tracer uptake using a pre-clinical PET scanner.Methods:Reconstructed images of a rodent tumor model bearing P22 carcinosarcoma injected with hypoxia tracer Copper-64-Diacetyl-bis (N4-methylthiosemicarbazone) (i.e. Cu-64 ATSM) were analyzed at 10 minute intervals till 60 minute post injection. Lesion maximum standardized uptake values (SUVmax) and SUVmax/background SUVmean (T/B) were recorded and investigated after application of multiple algorithm and reconstruction parameters to assess their influence on Cu-64 ATSM measurements and associated trends over time.Results:SUVmaxSUVmax or T/B between 2D FBP, exhibited convergence for OSEM reconstructions while ANOVA results showed a significant difference in SUVmax or T/B between 2D FBP, 2D OSEM, 3D OSEM and 3D OSEM MAP reconstructions across all time frames. SUVmax and T/B were greatest in magnitude for 2D OSEM followed by 3D OSEM MAP, 3D OSEM and then 2D FBP at all time frames respectively. Similarly SUVmax and T/B standard deviations (SD) were lowest for 2D OSEM in comparison with other algorithms.Conclusion:Significantly higher magnitude lesion SUVmax and T/B combined with lower SD were observed using 2D OSEM reconstruction in comparison with 2D FBP, 3D OSEM and 3D OSEM MAP algorithms at all time frames. Results are SUVmax or T/B between 2D FBP, consistent with other published studies however more specimens are required for full validation.

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Section: Discussionsupporting

confidence: 68%

Pre-clinical Positron Emission Tomography Reconstruction Algorithm Effect on Cu-64 ATSM Lesion Hypoxia

Sanghera

Wood²,

Sonoda³

et al. 2016

Mirt

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“…It is a neutral lipophilic molecule with a high cell membrane permeability and diffuses readily from the blood to surrounding cells. Once within the cell, it undergoes reduction only in hypoxic cells and becomes trapped intracellularly, but washes out rapidly from normal cells without any change (49). Copper has several positron-emitting radioisotopes which can be used.…”

Section: Hypoxia In Lung Cancermentioning

confidence: 99%

“…Clinical studies have shown that 64 Cu-ATSM PET is feasible in NSCLC and may play a role as a prognostic marker (37,(49)(50)(51)(52).…”

Section: Hypoxia In Lung Cancermentioning

confidence: 99%

The role of new PET tracers for lung cancer

et al. 2019

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18F-Fluorodeoxyglucose ( 18 F-FDG) positron emission tomography-computed tomography (PET/CT) is integral to the investigation and management of suspected or proven lung cancer (1) despite the nonspecific nature of the 18 F-FDG, which is a glucose analogue. An improved understanding in tumour biology and advances in therapeutic options has driven the need to better characterise tumours, and predict and monitor treatment response to new targeted cancer therapies. Some of the cancer-related cellular processes being investigated include tumour proliferation, amino acid metabolism, tumour hypoxia and angiogenesis. The majority of tracers being used to evaluate these processes remain restricted to preclinical and clinical research. There are also certain receptors which are expressed by specific cancers which can then be targeted by peptides, e.g. neuroendocrine tumours express somatostatin receptors which have an affinity to somatostatin analogues such as DOTA-peptides. 68 Ga-DOTA-peptides have an established role in PET imaging, including imaging of carcinoid tumours, but these are not specific to lung lesions.

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“…Recent work by Knight et al . compared the hypoxia selectivity and stability of the novel copper complex 64 Cu‐MTUBo, based on a tripodal monothiourea ligand, with that of 64 Cu‐ATSM . Similar to 64 Cu‐ATSM, 64 Cu‐MTUBo showed hypoxia selectivity in vitro , but time‐activity curves revealed faster tumour uptake of 64 Cu‐ATSM in vivo .…”

Section: Tumour Imaging With 64cumentioning

confidence: 99%

Radiocopper for the imaging of copper metabolism

Hueting

2014

Labelled Comp Radiopharmac

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The redox-active transition metal copper is an essential trace element for growth and development and serves as a structural or catalytic cofactor for many enzymes in a range of physiological processes. Mammalian copper homeostasis is tightly regulated, and an imbalance in copper metabolism is implicated in various pathological disorders. Radioactive copper isotopes, in particular (64) Cu (t1/2 = 12.7 h) and (67) Cu (t1/2 = 62.01 h), have made important contributions to the understanding of copper metabolism in health and disease. This review gives a brief account of how radiolabelled copper(II) salts and bioreductive copper complexes have been used to trace copper uptake, transport and efflux in vitro and in vivo. Recently, positron emission tomography (PET) has emerged as a noninvasive tool to image copper metabolism in living subjects and (64) Cu-PET is investigated for the study of copper-related neurological disorders, genetic diseases and cancer.

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Synthesis, characterisation and evaluation of a novel copper-64 complex with selective uptake in EMT-6 cells under hypoxic conditions

Cited by 9 publications

References 56 publications

Pre-clinical Positron Emission Tomography Reconstruction Algorithm Effect on Cu-64 ATSM Lesion Hypoxia

Pre-clinical Positron Emission Tomography Reconstruction Algorithm Effect on Cu-64 ATSM Lesion Hypoxia

The role of new PET tracers for lung cancer

Radiocopper for the imaging of copper metabolism

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